chr5-13718913-T-G

Variant names:

• chr5-13718913-T-G
• rs30169
• NM_001369.3:c.12468A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001369.3(DNAH5):​c.12468A>C​(p.Gly4156Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,612,042 control chromosomes in the GnomAD database, including 138,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G4156G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.40 (12470 hom., cov: 32)
  • Exomes 𝑓: 0.41 (126278 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.0460
• Publications: 19 publications found

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

DNAH5 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 5-13718913-T-G is Benign according to our data. Variant chr5-13718913-T-G is described in ClinVar as Benign. ClinVar VariationId is 178742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.046 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.12468A>C	p.Gly4156Gly	synonymous	Exon 72 of 79	NP_001360.1	Q8TE73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.12468A>C	p.Gly4156Gly	synonymous	Exon 72 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.12423A>C	p.Gly4141Gly	synonymous	Exon 72 of 79	ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61243 AN: 151888 Hom.: 12452 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.404

GnomAD2 exomes AF: 0.414 AC: 103983 AN: 251176 AF XY: 0.416

Gnomad AFR exome AF: 0.394

Gnomad AMR exome AF: 0.442

Gnomad ASJ exome AF: 0.418

Gnomad EAS exome AF: 0.411

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.415

Gnomad OTH exome AF: 0.416

GnomAD4 exome AF: 0.414 AC: 604683 AN: 1460036 Hom.: 126278 Cov.: 41 AF XY: 0.415 AC XY: 301515 AN XY: 726432

African (AFR) AF: 0.387 AC: 12945 AN: 33436

American (AMR) AF: 0.436 AC: 19504 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 10666 AN: 26126

East Asian (EAS) AF: 0.399 AC: 15838 AN: 39688

South Asian (SAS) AF: 0.454 AC: 39109 AN: 86222

European-Finnish (FIN) AF: 0.331 AC: 17696 AN: 53412

Middle Eastern (MID) AF: 0.436 AC: 2514 AN: 5766

European-Non Finnish (NFE) AF: 0.415 AC: 461313 AN: 1110336

Other (OTH) AF: 0.416 AC: 25098 AN: 60336

GnomAD4 genome AF: 0.403 AC: 61311 AN: 152006 Hom.: 12470 Cov.: 32 AF XY: 0.398 AC XY: 29576 AN XY: 74286

African (AFR) AF: 0.396 AC: 16425 AN: 41466

American (AMR) AF: 0.414 AC: 6321 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1439 AN: 3472

East Asian (EAS) AF: 0.431 AC: 2230 AN: 5170

South Asian (SAS) AF: 0.452 AC: 2168 AN: 4800

European-Finnish (FIN) AF: 0.317 AC: 3342 AN: 10548

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27996 AN: 67970

Other (OTH) AF: 0.407 AC: 860 AN: 2112

Alfa AF: 0.415 Hom.: 21076

Bravo AF: 0.410

Asia WGS AF: 0.447 AC: 1558 AN: 3478

EpiCase AF: 0.421

EpiControl AF: 0.433

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Primary ciliary dyskinesia (3)
-	-	3	Primary ciliary dyskinesia 3 (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.2
DANN	Benign	0.65
PhyloP100		0.046
Mutation Taster		=79/21	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs30169; hg19: chr5-13719022; COSMIC: COSV54212375;